Lin Ming-Cheng, Hwang Mei-Ting, Chang Han-Ging, Lin Chung-Sheng, Lin Gialih
Institute of Medicine, Department of Cardiology, Chung Shan Medical University Hospital, Taichung 402, Taiwan.
J Biochem Mol Toxicol. 2007;21(6):348-53. doi: 10.1002/jbt.20202.
Benzene-1,2-, 1,3-, and 1,4-di-N-substituted carbamates (1-15) are synthesized as the conformationally constrained inhibitors of acetylcholinesterase and mimic gauche, eclipsed, and anti-conformations of acetylcholine, respectively. All carbamates 1-15 are characterized as the pseudo substrate inhibitors of acetylcholinesterase. For a series of geometric isomers, the inhibitory potencies are as follows: benzene-1,4-di-N-substituted carbamate (para compound) > benzene-1,3-di-N-substituted carbamate (meta compound) > benzene-1,2-di-N-substituted carbamate (ortho compound). Therefore, benzene-1,4-di-N-substituted carbamates (para compounds), with the angle of 180 degrees between two C(benzene)-O bonds, mimic the preferable anti C-O/C-N conformers of acetylcholine for the choline ethylene backbone in the acetylcholinesterase catalysis.
苯 -1,2 -、1,3 - 和 1,4 - 二 -N - 取代氨基甲酸酯（1 - 15）被合成为乙酰胆碱酯酶的构象受限抑制剂，分别模拟了乙酰胆碱的 gauche、重叠和反式构象。所有氨基甲酸酯 1 - 15 均被表征为乙酰胆碱酯酶的假底物抑制剂。对于一系列几何异构体，其抑制效力如下：苯 -1,4 - 二 -N - 取代氨基甲酸酯（对位化合物）> 苯 -1,3 - 二 -N - 取代氨基甲酸酯（间位化合物）> 苯 -1,2 - 二 -N - 取代氨基甲酸酯（邻位化合物）。因此，在两个 C(苯)-O 键之间夹角为 180 度的苯 -1,4 - 二 -N - 取代氨基甲酸酯（对位化合物），在乙酰胆碱酯酶催化过程中，模拟了乙酰胆碱中胆碱乙烯主链更优的反式 C - O/C - N 构象。
